We plan to perform in vitro studies of platelets and of platelet membrane properties, utilizing various physicochemical methods for detection of platelet membrane potentials, membrane fluidities, and of alterations in intraplatelet cation concentrations. Utilizing these methods we will study the response of platelets to various stimulants of aggregation, such as thrombin, adenosine diphosphate and collagen, the platelet surface receptors for these aggregants and the mechanism by which the stimulus response is transmitted. Normal human platelets in platelet rich plasma, chromatographically washed platelets and platelet ghosts will be used for these studies. These investigations are of importance in understanding normal and disorder-perturbed responses of platelets to aggregation in vivo. Such aggregation is triggered in vitro by collagen, ADP, thrombin, epinephrine, aggregated immunoglobulins, foreign surfaces, etc. In vivo, the interaction between platelets and collagen marks the initiation of hemostasis. Adhesion of platelets to collagen is followed by platelet shape change, release, reversible aggregation and finally irreversible aggregation in the presence of fibrin. The mechanisms of each of these steps, as well as the specific components on the platelet surface and of the collagen moiety which are responsible for recognition and for the interaction remain unknown. Disorders in this interaction occur in a variety of diseases of the cardiovascular system (e.g., thrombosis, intravascular coagulation, atherosclerosis), of platelets (e.g., von Willebrand's disease, thrombasthenia, myeloproliferative disorders), and of collagen (e.g., Marfan's syndrome, rheumatoid arthritis) as well as in diseases such as cyrrhosis, and in reactions of the circulatory system to dialysis, to external pumping or to implants.